Practical Asymmetric Fluorination Approach to the Scalable Synthesis of New Fluoroaminothiazine BACE Inhibitors,Organic Process Research & Development

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Practical Asymmetric Fluorination Approach to the Scalable Synthesis of New Fluoroaminothiazine BACE Inhibitors
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-04-24 00:00:00 , DOI: 10.1021/acs.oprd.8b00069
Pablo Garcia-Losada ₁ , Mario Barberis ₁ , Yuan Shi ₂ , Erik Hembre ₂ , Carolina Alhambra Jimenez ₁ , Leonard L. Winneroski ₂ , Brian M. Watson ₂ , Chauncey Jones ₂ , Amy C. DeBaillie ₂ , Francisco Martínez-Olid ₁ , Dustin J. Mergott ₂

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Here we report an optimized protocol for the asymmetric introduction of a fluorine atom into a quaternary center facilitated by d-proline, Selectfluor^®, and trifluoroethanol. The synthesis proceeds over four steps starting from a chiral amino alcohol precursor and provides the desired enantiomer with no erosion of chiral purity and good diastereoselectivity. The process optimization allowed diastereoselective preparation of the key intermediate on a multigram scale.

中文翻译：

实用的不对称氟化方法可扩展合成新型氟氨基噻嗪BACE抑制剂

这里，我们报告不对称引入氟原子的成促进季中心的优化协议d -脯氨酸，的Selectfluor ^®，和三氟乙醇。从手性氨基醇前体开始，合成过程分四个步骤进行，提供了所需的对映异构体，而没有手性纯度的下降和良好的非对映选择性。通过工艺优化，可以以毫克级规模对关键中间体进行非对映选择性制备。

更新日期：2018-04-24

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